chrX-74739411-G-C

Position:

• chrX-74739411-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008537.3(NEXMIF):​c.4545C>G​(p.Asp1515Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: NEXMIF NM_001008537.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79

Genes affected

NEXMIF (HGNC:29433): (neurite extension and migration factor) An inversion on the X chromosome which disrupts this gene and a G-protein coupled purinergic receptor gene located in the pseudoautosomal region of the X chromosome has been linked to X linked cognitive disability.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.168903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXMIF	NM_001008537.3	c.4545C>G	p.Asp1515Glu	missense_variant	4/4	ENST00000055682.12	NP_001008537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXMIF	ENST00000055682.12	c.4545C>G	p.Asp1515Glu	missense_variant	4/4	1	NM_001008537.3	ENSP00000055682	P1
NEXMIF	ENST00000616200.2	c.4545C>G	p.Asp1515Glu	missense_variant	4/5	1		ENSP00000480284	P1
NEXMIF	ENST00000642681.2	c.*685C>G		3_prime_UTR_variant	3/3			ENSP00000495800

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1406261). This variant has not been reported in the literature in individuals affected with NEXMIF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1515 of the NEXMIF protein (p.Asp1515Glu). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.36	.;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.92	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.55	N;.
REVEL	Benign	0.12
Sift	Uncertain	0.015	D;.
Sift4G	Benign	0.29	T;T
Polyphen		0.49	P;P
Vest4		0.17
MutPred		0.20		Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP		0.36
MPC		0.57
ClinPred		0.66	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-73959246;